Femoral Neuropathy Secondary to Autosomal Dominant Polycystic Kidney Disease: A Case Report

Compressive femoral neuropathy is a disabling condition accompanied by difficulty in hip flexion and knee extension. It may result from retroperitoneal hematoma or bleeding, or from complications associated with pelvic, hip surgery, and renal transplants. A 55-year-old female with autosomal dominant polycystic kidney disease presented with proximal muscle weakness in lower extremities. The patient experienced recurrent renal cyst infection, with aggravated weakness during each event. Electromyography and nerve conduction study revealed bilateral femoral neuropathy. Computed tomography and magnetic resonance images were added to further identify the cause. As a result, a diagnosis of femoral neuropathy caused by enlarged polycystic kidney was made. Cyst infection was managed with antibiotics. Renal function was maintained by frequent regular hemodialysis. While avoiding activities that may increase abdominal pressure, rehabilitation exercises were provided. Motor strength in hip flexion and knee extension improved, and was confirmed via electrodiagnostic studies

REV1 Inhibition Enhances Radioresistance and Autophagy

SIMPLE SUMMARY: Cancer resistance to therapy continues to be the biggest challenge in treating patients. Targeting the mutagenic translesion synthesis (TLS) polymerase REV1 was previously shown to sensitize cancer cells to chemotherapy. In this study, we tested the ability of REV1 inhibitors to radiation therapy and observed a lack of radiosensitization. In addition, we observed REV1 inhibition to trigger an autophagy stress response. Because reduction of REV1 triggered autophagy and failed to radiosensitize cells, we hypothesize REV1 expression dynamics might link cancer cell response to radiation treatment through the potential induction of autophagy. ABSTRACT: Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations suggest REV1’s important role in determining cancer cell response to chemotherapy. Whether REV1 inhibition would similarly sensitize cancer cells to radiation treatment is unknown. This study reports a lack of radiosensitization in response to REV1 inhibition by small molecule inhibitors in ionizing radiation-exposed cancer cells. Instead, REV1 inhibition unexpectedly triggers autophagy, which is a known biomarker of radioresistance. We report a possible role of the REV1 TLS protein in determining cancer treatment outcomes depending upon the type of DNA damage inflicted. Furthermore, we discover that REV1 inhibition directly triggers autophagy, an uncharacterized REV1 phenotype, with a significant bearing on cancer treatment regimens

Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition

Colorectal cancer (CRC) is the third most prevalent form of cancer in the United States and results in over 50,000 deaths per year. Treatments for metastatic CRC are limited, and therefore there is an unmet clinical need for more effective therapies. In our prior work, we coupled high-throughput chemical screens with patient-derived models of cancer to identify new potential therapeutic targets for CRC. However, this pipeline is limited by (1) the use of cell lines that do not appropriately recapitulate the tumor microenvironment, and (2) the use of patient-derived xenografts (PDXs), which are time-consuming and costly for validation of drug efficacy. To overcome these limitations, we have turned to patient-derived organoids. Organoids are increasingly being accepted as a “standard” preclinical model that recapitulates tumor microenvironment cross-talk in a rapid, cost-effective platform. In the present work, we employed a library of natural products, intermediates, and drug-like compounds for which full synthesis has been demonstrated. Using this compound library, we performed a high-throughput screen on multiple low-passage cancer cell lines to identify potential treatments. The top candidate, psymberin, was further validated, with a focus on CRC cell lines and organoids. Mechanistic and genomics analyses pinpointed protein translation inhibition as a mechanism of action of psymberin. These findings suggest the potential of psymberin as a novel therapy for the treatment of CRC

On valency problems of Saxl graphs

Let $G$ be a permutation group on a set $\Omega$ and recall that a base for $G$ is a subset of $\Omega$ such that its pointwise stabiliser is trivial. In a recent paper, Burness and Giudici introduced the Saxl graph of $G$, denoted $\Sigma(G)$, with vertex set $\Omega$ and two vertices adjacent if they form a base. If $G$ is transitive, then $\Sigma(G)$ is vertex-transitive and it is natural to consider its valency (which we refer to as the valency of $G$). In this paper we present a general method for computing the valency of any finite transitive group and we use it to calculate the exact valency of every primitive group with stabiliser a Frobenius group with cyclic kernel. As an application, we calculate the valency of every almost simple primitive group with an alternating socle and soluble stabiliser and we use this to extend results of Burness and Giudici on almost simple primitive groups with prime-power or odd valency

Hong: Weaving Aspects into Real-Time Operating System Design using ObjectOriented Model Transformation, this volume (WORDS 2003

Despite of the proliferation of object-oriented and component technology, their application to real-time operating systems (RTOS) has been limited since most design concerns in RTOSes crosscut software components and these are critical to deliver required performance and functionality. Aspect-Oriented Programming (AOP) is a very effective means to solve the crosscutting problem. However, we have observed the following limitations of the current AOP framework: (1) the current text-based AOP languages cannot clearly show how aspects are weaved together, (2) their granularity is too coarse to capture all aspects in an RTOS, (3) it is difficult to control the weaving process, since aspect weavers are usually hard-coded. In this paper, we propose a new AOP framework that provides (1) a graphical aspect programming environment that visualizes aspects, crosscutting classes, and method structures, (2) a new aspect model that supports a sub-method level granularity where an aspect is defined as a set of classes, and (3) an aspect weaving process specified by an object-oriented meta-model transformation. Since our aspect-oriented programming framework improves the expressiveness of the crosscutting concerns of RTOSes and automates aspect weaver generation, it can enhance RTOS customization. 1